Summary Alzheimer's disease (AD) is characterized by cognitive decline and 5–10 fold increased seizure incidence. How seizures contribute to cognitive decline in AD or other disorders is unclear. We show spontaneous seizures increase expression of ΔFosB, a highly stable Fos-family transcription factor, in the hippocampus of an AD mouse model. ΔFosB suppressed expression of the immediate early gene c-Fos, which is critical for plasticity and cognition, by binding its promoter and triggering histone deacetylation. Acute HDAC inhibition or inhibition of ΔFosB activity restored c-Fos induction and improved cognition in AD mice. Administration of seizure-inducing agents to nontransgenic mice also resulted in ΔFosB-mediated suppression of c-Fos, suggesting this mechanism is not confined to AD mice. These results explain observations that c-Fos expression increases after acute neuronal activity but decreases with chronic activity. Moreover, these results indicate a general mechanism by which seizures contribute to persistent cognitive deficits even during seizure-free periods.

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SUMMARY Adult hippocampal neurogenesis has been reported to be decreased, increased, or not changed in Alzheimer’s disease (AD) patients and related transgenic mouse models. These disparate findings may relate to differences in disease stage, or the presence of seizures, which are associated with AD and can stimulate neurogenesis. In this study, we investigate a transgenic mouse model of AD that exhibits seizures similarly to AD patients and find that neurogenesis is increased in early stages of disease, as spontaneous seizures became evident, but is decreased below control levels as seizures recur. Treatment with the antiseizure drug levetiracetam restores neurogenesis and improves performance in a neurogenesis-associated spatial discrimination task. Our results suggest that seizures stimulate, and later accelerate the depletion of, the hippocampal neural stem cell pool. These results have implications for AD as well as any disorder accompanied by recurrent seizures, such as epilepsy.

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The survival rate was high, compared with rates reported after cesarean section, and short-term fertility rate was similar to those reported for mares that had a controlled vaginal delivery or cesarean section. Fetotomy performed by a skilled veterinarian on a nonviable fetus should be considered as a means of quick and safe correction of dystocia that does not necessarily impair short-term fertility in affected mares.

Pilot experimental study on amniotic epithelial mesenchymal cell transplantation in natural occurring tendinopathy in horses. Ultrasonographic and histological comparison were grafted, in sterile conditions and under ultrasound control, into the most damaged area. Ultrasound controls were performed at 30, 60, 90, 120, 150 and 180 days after cells implantation; after horse euthanasia (180 days) tendon samples were collected and submitted to histological examination (cellularity, extracellular matrix fiber organization, blood vessels). Results: at baseline, in the acute cases, the ultrasound exam showed a focal, dis-homogeneous, hypo-echoic area into the superficial digital flexor tendon, with loss of the normal fibrillar pattern, while in the chronic cases the damaged tendon area appeared thickened and completely hyperechoic. At the final follow-up tendon echotexture was more regular, the cross-sectional area similar to the contra-lateral limb, and the collagen fibers were oriented in parallel to the longitudinal axis of the tendon both in the acute and chronic cases, suggesting a positive healing response. These findings were supported by the histological analyses which showed an almost complete restoration of normal tendon architecture with an optimal alignment of tendon fibers. Conclusions: the present pilot study supports the hypothesis that amniotic epithelial cells are provided of an excellent healing potential and shows a very good correlation between the ultrasound findings and the histologic features.

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

Today a great deal of research is focused on the development of new extenders that allow the refrigeration and maintenance of rabbit semen for a longer period of time. In this study, semen diluted with 3 different extenders (A, B, and C) and stored at two different temperatures (4°C and 38°C) were evaluated using both laboratory and in vivo tests. The best results were obtained with extender C (INRA 96) which, in the first 10 h of the test at 4°C, displayed about 80% higher motility compared to the other two extenders and preserved optimal seminal fluid motility for over 34 h after dilution. In the test at 38 °C, the motility of semen diluted with extender C was 52% in the fifth h vs 21% of the semens diluted with extenders A (Lepus) and B (Verdunnungsmischung). Another test involved artificial insemination (AI) of 1800 lactating does using refrigerated semen diluited with the extenders under study. The fertility rate and litter size obtained with semen diluted with extender C was higher (78.1% and 8.65, respectively) than those obtained with extenders A (71.2% and 8.15, respectively) and B (71.05% and 8.13, respectively) in both parallel and sequential tests. In conclusion, extender C offers greater vitality and motility to rabbit spermatozoa, thus higher fertility rates to rabbits does.